C018 – Experimental Neurology of Parkinson´s Disease

Objectives

For years our work has focused on studying the cellular and molecular mechanisms responsible for neurodegeneration in Parkinson’s disease, identifying key points for therapeutic intervention. We aim to transform this knowledge into effective neuroprotective strategies that preserve the function of dopaminergic neurons and facilitate their translation to clinical practice.

We work to validate new therapeutic targets, such as the cerebral renin-angiotensin system and pathological alpha-synuclein, and to promote high-precision cell models, based on stem cells, that accelerate the development of drugs and neuronal replacement strategies.

We also seek to prevent treatment-related complications (such as dyskinesias) and develop early biomarkers that allow intervention in the initial stages of the disease, when it is still possible to modify its evolution.

Lines of research

• Deciphering the molecular mechanisms of neurodegeneration in Parkinson’s disease
• Development of neuroprotective strategies with translational potential
• Study of the cerebral renin-angiotensin system as a therapeutic target
• Characterization of the pathogenicity of alpha-synuclein
• Development of precision cell models based on stem cells
• Identification of mechanisms involved in treatment-induced dyskinesias
• Identification of early biomarkers of neurodegeneration

Papel de astrocitos y oligodendrocitos en degeneración dopaminérgica. Regulación por el sistema renina-angiotensina cerebral – ASTROLIGANG
Project code: PID2024-155522OB-I00
Financial entity: Agencia Estatal de Investigación
Duration: 2025-2028
Principal investigator: Rita Valenzuela Limiñana

Vesículas extracelulares como mecanismo de progresión de la degeneración neuronal dopaminérgica y biomarcadores deneurodegeneración EVsNDG
Project code: PID2023-150743OB-I00
Financial entity: Agencia Estatal de Investigación
Duration: 2024-2027
Principal investigator: Ana Isabel Rodríguez-Pérez

Alteraciones en la neurogénesis en enfermedad de Parkinson y COVID-19: Interacciones entre sistema renina-angiotensina, dopamina yADAM17 como nuevas dianas terapéuticas
Project code: PID2022-137079NB-I00
Financial entity: Agencia Estatal de Investigación
Duration: 2023-2026
Principal investigator: Jeanette Rodríguez Pallares

Métodos in vitro alternativos humanos para el estudio de enfermedades neurodegenerativas (AlterNED)
Project code: PLEC2022-009401
Financial entity: Instituto de Salud Carlos III
Duration: 2022-2025
Principal investigator:

Red de Investigación en Terapias Avanzadas
Project code: RD21/0017/0031
Financial entity: Instituto de Salud Carlos III
Duration: 2022-2024
Funding: 89 997,60 EUR
Principal investigator: José Luis Labandeira García

Red de Investigación en Terapias Avanzadas: RICORS TERAV
Project code: RD21/0017/0031
Financial entity: Instituto de Salud Carlos III
Duration: 2022-2024
Principal investigator:

Sistema renina-angiotensina cerebral y enfermedad de parkinson. Interacciones con otros mecanismos principales involucrados en la degeneración dopaminérgica
Project code: PID2021-126848NB-I00
Financial entity: Agencia Estatal de Investigación
Duration: 2022-2026
Principal investigator:

Neurodegeneración ligada a la neuromelanina en la enfermedad de Parkinson: Implicaciones mecanísticas, diagnósticas y terapéuticas
Project code: PI2020/09
Financial entity: Instituto de Salud Carlos III
Duration: 2021-2022
Funding: 315 000 EUR
Principal investigator: José Luis Labandeira García Miquel Vila (coord.)

Síndrome Metabólico y Riesgo de Enfermedad de Parkinson: Estudio Experimental y Clínico de los Mecanismos implicados
Project code: PI20/00345
Financial entity: Instituto de Salud Carlos III
Duration: 2021-2023
Funding: 179 080 EUR
Principal investigator: Ana Isabel Rodríguez Pérez

Clarificación del efecto beneficioso o perjudicial de los tratamientos con Sartanes, IECAS e ibuprofeno sobre la vulnerabilidad a la infección y el agravamiento de la enfermedad Covid-19
Project code: IN845D 2020/20
Financial entity: Axencia Galega de Innovación
Duration: 2020-2022
Funding: 121 878 EUR
Principal investigator: José Luis Labandeira García

Consolidación e estructuración 2018 GRC GI- 1337 Grupo de Neurobiología Molecular y Celular de la Enfermedad de Parkinson (Neurolab)
Project code: ED431C 2018/10
Financial entity: Axencia Galega de Innovación
Duration: 2019-2021
Funding: 280 000 EUR
Principal investigator: José Luis Labandeira García

Effects of peripheral Processes on Neuroinflammation and Neurodegeneration. Role of the renin angiotensin system
Project code: RTI2018-098830-b-i00
Financial entity: Agencia Estatal de Investigación
Duration: 2019-2021
Funding: 326 700 €
Principal investigator: José Luis Labandeira García

Estudio Experimental y Clínico para identificación de marcadores de Mecanismos de Progresión de la enfermedad de Parkinson y posibles dianas terapéuticas para Neuroprotección
Project code: PI17/00828
Financial entity: Instituto de Salud Carlos III
Duration: 2018-2021
Funding: 105 270,00 €
Principal investigator: Ana Isabel Rodríguez Pérez

Red Terapia Celular (TerCel)
Project code: RD16/0011/0016
Financial entity: Instituto de Salud Carlos III/FEDER-INTERREG
Duration: 2017-2021
Funding: 240 245,50 €
Principal investigator: José Luis Labandeira García

Sistema Renina Anxiotensina cerebral en neuroinflamación y degeneración dopaminérgica. Más alla del eje AII/AT1/NADPH-Oxidasa. Excelencia 2015
Project code: 2015-PN055
Financial entity: Ministerio de Economía y Competitividad
Duration: 2016-2018
Funding: 296 450 EUR
Principal investigator: José Luis Labandeira García

• Camacho-Meño L, Labandeira CM, Bravo SB, Torres MV, Bejr-Kasem H, Molina-Crespo A, Atienza M, Lanciego JL, Cantero JL, Kulisevsky J, Labandeira-Garcia JL, Rodriguez-Perez AI. Brain-derived extracellular vesicle proteomics reveals neuroprotection induced by the ARB candesartan in Parkinson’s disease patients. NPJ Parkinsons Dis. 2025 Dec 10;12(1):19. doi: 10.1038/s41531-025-01230-6. PMID: 41366251; PMCID: PMC12804683.
• Lage L, Rodriguez-Perez AI, Labandeira-Garcia JL, Dominguez-Meijide A. Fasudil inhibits α-synuclein aggregation through ROCK-inhibition-mediated mechanisms. Neurotherapeutics 2025 Mar;22(2):e00544. doi:10.1016/j.neurot.2025.e00544. Epub 2025 Feb 5. PMID: 39915220; PMCID:PMC12014416.
• Quijano A, Rodriguez-Perez AI, Costa-Besada MA, Lopez-Lopez A, Guerra MJ, Labandeira-Garcia JL, Valenzuela R. Modulation of Mitochondrial Dynamics by the Angiotensin System in Dopaminergic Neurons and Microglia. Aging Dis. 2024 Oct 22;16(5):3180-3203. doi: 10.14336/AD.2024.0981. PMID: 39500352; PMCID: PMC12339132.
• Rodríguez-Pérez AI, Garrido-Gil P, García-Garrote M, Muñoz A, Parga JA, Labandeira-García JL, Rodríguez-Pallares J. Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson’s disease models. Stem Cell Res Ther. 2024 May 12;15(1):138. doi:10.1186/s13287-024-03751-y. PMID: 38735991; PMCID: PMC11089721.
• Labandeira-Garcia JL, Labandeira CM, Guerra MJ, Rodriguez-Perez AI. The role of the brain renin-angiotensin system in Parkinson´s disease. Transl Neurodegener. 2024 Apr 15;13(1):22. doi: 10.1186/s40035-024-00410-3. PMID: 38622720; PMCID: PMC11017622.
• Lage L, Rodriguez-Perez AI, Villar-Cheda B, Labandeira-Garcia JL, Dominguez-Meijide A. Angiotensin type 1 receptor activation promotes neuronal and glial alpha-synuclein aggregation and transmission. NPJ Parkinsons Dis. 2024 Feb 17;10(1):37. doi: 10.1038/s41531-024-00650-0. PMID: 38368444; PMCID: PMC10874459.
• González-Vila A, Luengo-Mateos M, Silveira-Loureiro M, Garrido-Gil P, Ohinska N, González-Domínguez M, Labandeira-García JL, García-Cáceres C, López M, Barca-Mayo O. Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner. Nat Commun. 2023 Dec 9;14(1):8175. doi: 10.1038/s41467-023-44039-8. PMID: 38071352; PMCID: PMC10710518.
• Pedrosa MA, Labandeira CM, Valenzuela R, Quijano A, Sanchez-Andrade M, Suarez-Quintanilla JA, Lanciego JL, Labandeira-Garcia JL, Rodriguez-Perez AI. AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability. Brain Behav Immun. 2023 Feb;108:255-268. doi: 10.1016/j.bbi.2022.12.009. Epub 2022 Dec 16. PMID: 36535607.

Cell and Molecular Neurobiology of Parkinson’s Disease | CiMUS